New dihydrotriazine derivatives and a process for their manufacture



United States Patent 3,105,074 NEW DIHYDRQTRIAZINE DERIVATIVES AND A PRGCESS FQR THETR MANUFACTURE Patrick Maniaiis, Cheam, England, assignor to Vitamins Limited, London, England, a British company No Drawing. Filed Nov. 21, 1&61, Ser. No. 1543352 Claims priority, application Great Britain Nov. 29, 1960 1 Qlaim. (Cl. 260-2493) This invention relates to substances useful as bactericidal agents.

United States Patent No. 2,976,288 describes claims substituted triazines of the generalformula:

and

NE NH (II) in which R has the meaning given above, with a carbonyl compound of i e general formula:

where R has the meaning given above in the presence of an acid catalyst.

According to this invention an improved process has been discovered for making the compounds of Patent No. 2,976,288 which can also be used for producing further novel substituted triazines useful as bactericidal agents.

Accordingly the present invention provides a process for the preparation of compounds of the general formula:

lTHz

aiasaii Patented Sept. 24, 1963 and salts thereof in which Y is the hydrogen atom or an alkyl radical or a carbocyclic or heterocyclic ring system such as a benzene, naphthalene, phenanthrene, anthracene, pyrene or quinoline ring, any of which may be substituted by a chlorine or bromine atom or a methyl radical, wherein 4,6-diamino-l,2-dihydro-2,2-dimethyl-lhydroxy-l,3,5-triazine is reacted with a halide of the general formula YCH Z in which Z is a chlorine, bromine or iodine atom and Y has the meaning given above in an inert solvent or diluent such as dimethylformamide or a lower alcohol.

The present invention also includes the novel com- .pounds of the general formula (IV) in which Y is a phenanthrene, anthracene, pyrene or quinoline ring, any of which may be substituted by achlorine or bromine atom or a methyl radical.

The preparation of 4,6-diamino-l,2-dihydro-2,2-dimethyl-1-hydroxy-L3,S-triazine is described in application Serial No. 154,050 of even date herewith and now abandoned.

The process of the present invention is especially useful in that it is applicable both to extremely labile halomethyl derivatives such as 9- bromomethyl anthracene and to less labile derivatives such as n-decyl bromide. Under the conditions of reaction, only the hydrogen of the hydroxyl group in 4,6-diamino-l,2-dihydro-2,2 dimethyl-l-hydroxy-l,3,5-triazine undergoes replacement, the amino groups being unchanged. The reaction is preferably conducted in the absence of extraneous base, but if required one equivalent of sodium or sodium hydroxide may be used per one mole of 4,6-diamino-1,2- dihydro-2,2-dimethyl-l-hydroxy-1,3,5-triazine. For convenience the hydrochloride of 4,6-diamino-1,2-dihydro- 2,2-dimethyl-1-hydroxy-1,3,5-triazine is generally employed from which the free base is obtained by treatment with ethanolic sodium hydroxide.

The following examples, in which the parts are by weight, illustrate the invention.

Example 1 1-hydroxy-4,6-diamino 1,2 dihydro 2,2-dimethyl- 1,3,5-triazine hydrochloride (19.4 parts) in ethanol (250 parts) was treated with sodium hydroxide (4.0 parts) in ethanol (20 parts). The sodium chloride which separated was removed by filtration and the filtrate evaporated to dryness. The residual solid was suspended in dimethylformamide (200 parts), treated with methyl iodide (17 parts) and stirred at room temperature for 1 hour, then heated for 1 hour and evaported. The residual solid was stirred with a little Water, and the insoluble product crystallized from ethanol-ether. 4,6-diamino-1,2- dihydr0-2,2-dimethyl-l-methoxy-1,3,5-triazine hydroiodide (21 parts) separated in needles from ethanol-ether, MP. 217-218" C.

Example 2 l-hydroxy 4,6 diarnino 1,2 dihydro-2,2-dimethyl- 1,3,5-triazine hydrochloride (19.4 parts) was converted into the base as in Example 1 and the base suspended in dimethylformamide (200 parts). n-Decyl bromide (23 parts) was added and the mixture heated for 30 3 minutes with stirring. After working up as in Example 1, 4,6-diamino-1,2 dihydro-2,2 'limethyl-l-n decyloxy- 1,3,5-triazine hydrobromide was obtained as needles from ethanol-ether, 193-194 C. (16 parts).

Example 3 4,6-diamino-1,2-dihydro-2,2-dimethyl-l-hydroxy 1,3,5- triazine hydrochloride (7 parts) dissolved in ethanol (150 parts) was treated with sodium metal (1.7 parts) in ethanol parts) and the mixture stirred at C. 2- brornomethylphenanthrene (9.5 parts) was added and stirring continued for 4 hours. Ethanolic hydrogen chloride was added, the insoluble portion removed by filtration and the filtrate evaporated to give a solid. Crystallisation from ethanol-acetone gave 4,6-diamino-1,2-dihydro-2,2-dimethy1 1 (2-phenanthrylmethoxy 1,3,5- triazine hydrochloride, needles, M.P. 223 C. (103 parts).

Example 4 Example 5 4,6-diamino-1,2-dihydro-2,2 dimethyl-l hydroxy-triazine (2.6 parts) suspended in dimethylformamide (50 parts) was treated with 8-bromomethy-lquinoline (3.65 parts) and heated at 85 C. for 15 minutes. Evaporation of the solution left a solid which was crystallised from aqueous ethanol to give 4,6-diarnino-1,2-dihydro-2,2-dimethyl-l-(8-quinolylmethoxy)-1,3,5 triazine hydrobromide as needles, M.P. 251252 C. (3.7 parts).

The following additional compounds of the present invention have been prepared by methods analogous to those of tie preceding examples. These compounds are of the general formula (IV), the values of Y being as stated in the table.

Example IV) Y Base or Salt M.P., C.

p-Tertiary-butylphenyl. Base 246 3,4-Dichlor0phenyl Hydrochloride. 227 l-Naphthyl Hydrobromide 205 9- 2-Naphthyl do 219 10 1-Bromo-2-naphthy1 Hydrochloride; 217 11- do Hydrobroruide 217 12- 1-Bromo-4-naphthyl Hydrochloride 225 13- Q-PhenanthryL d 235 14 l-PhenanthryL 228 15- 3-Phenanthryl- 214 16 do 230 17 Q-Bromo-lO-anthryl- 219 18 3-Pyreny1... do 238 S-QuinolyL Dihydro chloride. 242 2-Ql1in0lyl Hydrobromide. 186 d-Methoxycarbonyldo 219. 5-220. 5

phenyl. 22 2-"VIethoxyearbony1- .-do r 225-228 phenyl. 1-Chloro-2-naphthyl do 223-224 24- 3,4-Diel1lorophenyl Saccharinate 183 25- l-Naphthyl 183-185 do 202-203 Succinate 225-226 Acid phthalate 195 Phosphate 210-211 p-Nitrobenzoate 230-232 Stearate 149-150 Saceharinate- 207 Acetate 1G0 Acid maleate 195 p-Nitrobenzoatem" 218 Mandela/Be 182-183 N -Acetylglyeinate.. 194-195 C :o naphth Saecharinate 185-186 39- 1-Bron1o-2-naphthyl Acetate 186-187 40 2-Phenenthryl Saccharinate. 186-188 41 8-Quinolyl o 234-235 I claim A process for the preparation of a compound selected from the group consisting of compounds of the formula:

NH: Y--OH2--ON N CHa7C /C-NH2 CH3 N/ and salts thereof in which Y is selectedfrom the group consisting ofhydrogen, alkyl radicals of up to fourteen carbon atoms and phenyl, naphthyl, phenanthryl, pyrenyl and quinolyl radicals, and said radicals substituted by one of the substituents chlorine, bromine, lower alkyl and car bomethoxy, which comprises reacting 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-hydroxy-1,3,5-triazine with a halide of the formula YCH Z in which Z is a halogen atom having an atomic Weight greater than 35 and Y has the meaning hereinbefore given in an inert reaction medium and recovering the compound so produced.

References Cited in the file of this patent UNITED STATES PATENTS Wolf Oct. 11, 1955 Green et al Mar. 21, 1961 OTHER REFERENCES 

